"Because no one has ever connected LRP6 to proliferation in tumors, we believe we may have identified a new oncogene," says Guojun Bu, Ph.D., associate professor of pediatrics and of cell biology and physiology. The findings will be reported in the December 2nd issue of the journal Oncogene. The article is available online Oct. 25.
"In several types of human cancer, such as breast and colon cancer, a key cell signaling pathway that regulates cell growth and development is overactive because a gene coding for a pathway component has mutated," Bu says.
Increased signal activity from this pathway can lead to abnormal cell proliferation and ultimately to cancer, but researchers have been unable to identify the pathway component responsible for certain types of cancer such as breast cancer. "We believe LRP6 may be the missing link, the long-sought component that turns up the activity of this signaling pathway," Bu says.
To uncover LRP6's role in cancer, Bu's team took slow-growing cancer cells and altered the LRP6 gene so that it made more of the protein. They found that the cancer cells began proliferating more rapidly as a result. When the researchers introduced these aggressive cells into mice, the animals developed tumors twice as large as those caused by the original, slow-growing cancer cells.
Having seen the effect of high-levels of LRP6 in laboratory experiments, Bu and his team looked for higher-than-normal LRP6 gene activity in human tumor samples. "We used patient-matched tumor specimens from the Siteman Cancer Center," Bu says. "We found both colon and brea
Contact: Gwen Ericson
Washington University School of Medicine